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British Journal of Pharmacology Dec 1983Adenosine added to human basophils before anti-IgE challenge inhibited histamine release, whereas addition after challenge potentiated release. Peak responses for the...
Adenosine added to human basophils before anti-IgE challenge inhibited histamine release, whereas addition after challenge potentiated release. Peak responses for the two effects occurred 15 min before and after challenge respectively. The effects of adenosine on histamine secretion were dose-related over concentration ranges of 1-100 microM for inhibition and 0.01-1 microM for potentiation. The capacity of adenosine to inhibit and potentiate histamine secretion was inversely related to the strength of immunological challenge. The ability of theophylline (50 microM) to inhibit and dipyridamole (1 microM) to enhance slightly adenosine-induced responses, and the differing pharmacological effect of 2',5'-dideoxyadenosine suggested that adenosine's effects on basophil histamine secretion were mediated by stimulation of cell surface adenosine receptors. The order of potency of adenosine and its analogues L- and D- N6-phenylisopropyladenosine (PIA) and 5'-N-ethylcarboxamideadenosine (NECA) in inhibiting and potentiating IgE-dependent histamine release from basophils indicated that both responses were mediated by stimulation of the adenosine A2-receptor subtype. The capacity of adenosine to cause a transient increase of cyclic AMP levels in 40-70% basophil-enriched leucocytes confirmed the association between stimulation of A2-receptors and activation of adenylate cyclase.
Topics: Adenosine; Basophils; Cyclic AMP; Dipyridamole; Histamine Release; Humans; Immunoglobulin E; In Vitro Techniques; Receptors, Purinergic; Theophylline; Time Factors
PubMed: 6085948
DOI: 10.1111/j.1476-5381.1983.tb10063.x -
Neuroscience Letters Jan 2004This study investigated the effect of adenosine in the forced swimming test (FST) and the tail suspension test (TST) in mice, and the contribution of adenosine A1 and...
This study investigated the effect of adenosine in the forced swimming test (FST) and the tail suspension test (TST) in mice, and the contribution of adenosine A1 and A2A receptors to adenosine's antidepressant-like effect. The immobility time in the FST was reduced by adenosine given either by i.p. (5-10 mg/kg) or i.c.v. (0.01-10 microg/site) route. Adenosine (1-10 mg/kg, i.p.) also produced an antidepressant-like effect in the TST. No treatment affected locomotion in an open-field. The anti-immobility effect of adenosine (10 mg/kg, i.p.) in the FST was prevented by i.p. pretreatment of mice with caffeine (3 mg/kg), DPCPX (2 mg/kg) and ZM241385 (1 mg/kg). CHA (0.05 mg/kg, i.p.) and DPMA (1-5 mg/kg, i.p.) also produced an antidepressant-like effect in the FST. This is the first report of an antidepressant-like effect of adenosine in mice, apparently mediated through an interaction with A1 and A2A receptors.
Topics: Adenosine; Animals; Antidepressive Agents; Caffeine; Depressive Disorder; Disease Models, Animal; Female; Male; Mice; Motor Activity; Receptor, Adenosine A1; Receptor, Adenosine A2A; Stress, Psychological; Triazines; Triazoles; Xanthines
PubMed: 14729225
DOI: 10.1016/j.neulet.2003.10.040 -
Journal of Pharmaceutical and... Jul 1998Using liquid chromatography the stability of adenosine in aqueous solution was investigated at five different temperatures, namely 4, 22, 37, 60 and 72 degrees C over a...
Using liquid chromatography the stability of adenosine in aqueous solution was investigated at five different temperatures, namely 4, 22, 37, 60 and 72 degrees C over a period of 6 months. At the three lowest temperatures, the initial concentration of the product was not altered, at the highest temperatures there was a significant decrease. From these data the shelf life (t90) at room temperature was estimated to be at least 5 years.
Topics: Adenosine; Chromatography, Liquid; Drug Stability; Hydrogen-Ion Concentration; Solutions; Temperature; Time Factors
PubMed: 9656152
DOI: 10.1016/s0731-7085(97)00206-9 -
Medical Hypotheses Oct 1982Adenosine and its analogs depress the firing of neurons in various brain regions. The primary mode of action of adenosine in exerting this action appears to be the...
Adenosine and its analogs depress the firing of neurons in various brain regions. The primary mode of action of adenosine in exerting this action appears to be the depression of calcium entry, thus decreasing presynaptic neurotransmitter release. Adenosine uptake inhibitors and adenosine deaminase inhibitors potentiate the depressant actions of adenosine. Caffeine and theophylline, methylxanthines, antagonize these actions. Adenosine is therefore likely to be released and to exert an ongoing modulation of the neuron excitability in the intact brain. Adenosine uptake by nerve terminals appears to be important in regulating the extracellular concentration of adenosine and thus of adenosine's action. A number of groups of centrally active sedative, anxiolytic and anticonvulsant drugs inhibit adenosine uptake by brain synaptosomal preparations. It is proposed that these agents exert their sedative effects by inhibiting adenosine uptake and thus potentiating depressant actions by locally released adenosine on neuronal activity.
Topics: Adenosine; Animals; Antipsychotic Agents; Arousal; Brain; Caffeine; Diazepam; Hypnotics and Sedatives; Phenothiazines; Rats; Receptors, Cell Surface; Receptors, Purinergic; Synapses; Synaptic Transmission; Synaptosomes; Theophylline
PubMed: 6130465
DOI: 10.1016/0306-9877(82)90074-3 -
Recenti Progressi in Medicina 1989Adenosine has been found to contract human bronchial smooth muscle in vitro and to induce bronchoconstriction in asthmatic patients when administered by inhalation. The... (Review)
Review
Adenosine has been found to contract human bronchial smooth muscle in vitro and to induce bronchoconstriction in asthmatic patients when administered by inhalation. The importance of adenosine for bronchial tone and bronchial reactivity is still unclear. Adenosine seems unlikely to cause bronchoconstriction by a non-specific irritant effect. Some evidence suggests that the action of adenosine relates to a specific pharmacologic activity. Bronchoconstriction induced by adenosine is antagonized by theophylline and is potentiated by dipyridamole. Therapeutic concentrations of theophylline exhibit specificity for adenosine's bronchoconstrictor activity supporting the concept that the bronchospastic effect of adenosine is mediated through stimulation of cell surface receptors. Stimulation of afferent receptors producing vagally mediated reflex seems unlikely. A further explanation of adenosine bronchoconstriction is a release of mediators through potentiation of ongoing mediator release from bronchial luminal mast-cells.
Topics: Adenosine; Asthma; Bronchial Spasm; Humans
PubMed: 2682852
DOI: No ID Found -
The Journal of Pharmacology and... Apr 1995The relatively selective adenosine A1 agonists N6-cyclohexy-ladenosine (CHA), R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA) and S(+)-N6-(2-phenylisopropyl)adenosine...
The relatively selective adenosine A1 agonists N6-cyclohexy-ladenosine (CHA), R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA) and S(+)-N6-(2-phenylisopropyl)adenosine (S-PIA); the A2a agonist 2-p-carboxyethyl)phenethyl-amino-5'-N-ethylcarbox-amidoadenosin e (CGS-21680) and the nonselective A2 agonist 2-phenylaminoadenosine (CV-1808) were evaluated in vivo for their effects on aqueous humor dynamics and in vitro for their action on 3H-norepinephrine release and cAMP accumulation in the isolated iris/ciliary body. These studies demonstrated that adenosine agonists can modulate intraocular pressure (IOP). Except for CV-1808, the topical administration of adenosine agonists produced a unilateral dose-related reduction in IOP with a potency order of R-PIA = CHA > CGS-21680 > S-PIA > CV-1808. Although CV-1808 did not lower IOP, it did induce a significant dose-dependent rise in IOP. Neither the reduction in IOP induced by R-PIA nor the rise in IOP induced by CV-1808 was affected by surgical removal of the superior cervical ganglion. However, the adenosine agonist-induced reduction in IOP was associated with a significant decrease in aqueous flow. In vitro studies demonstrated that the adenosine agonists did not alter the evoked release of 3H-norepinephrine; however, they were effective in suppressing the accumulation of cAMP, and this response was blocked by pretreatment with the antagonist 8-cyclopentyl-1,3-dimethylxanthine. These studies provide evidence that adenosine agonists lower IOP by activating postjunctional adenosine A1 receptors. This response is associated with a reduction in aqueous flow and the modulation of cAMP in the iris/ciliary body.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adenosine; Animals; Cyclic AMP; Intraocular Pressure; Norepinephrine; Phenylisopropyladenosine; Purinergic P1 Receptor Agonists; Rabbits; Receptors, Purinergic P1
PubMed: 7714784
DOI: No ID Found -
Hearing Research 1987Adenosine has been implicated in neuromodulation in the central nervous system [(1985) Annu. Rev. Neurosci. 8, 103-124]. Its mechanism of action is thought to be a...
Adenosine has been implicated in neuromodulation in the central nervous system [(1985) Annu. Rev. Neurosci. 8, 103-124]. Its mechanism of action is thought to be a receptor-mediated inhibition of a transmitter release. To assess adenosine's role as a neuromodulator in the vestibular periphery, spontaneous activity of the afferent fibers in the ampullar nerve of the semicircular canal, in vitro, was used as the dependent variable. Afferent firing has been previously shown to depend on transmitter release by the hair cells [(1985) Brain Res. 330, 1-9]. Adenosine was shown to inhibit firing rate; the adenosine antagonist theophylline was shown to increase firing rate; the enzyme adenosine deaminase, which catabolizes adenosine to inosine, was shown to increase firing rate; the adenosine uptake inhibitor dipyridamole was shown to decrease firing rate; and adenosine was shown to be released from the isolated semicircular canal by electrical stimulation. All these findings are internally consistent and unreservedly support the hypothesis that adenosine has a neuromodulatory role in neurotransmission in the semicircular canal.
Topics: Adenosine; Animals; Auditory Pathways; Auditory Perception; Hair Cells, Auditory; Neural Inhibition; Rana pipiens; Semicircular Canals; Synapses; Synaptic Transmission; Vestibular Nerve
PubMed: 2824422
DOI: 10.1016/0378-5955(87)90139-0 -
Proceedings of the National Academy of... Sep 1992Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells. We have used...
Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells. We have used whole cell recording from these cells in slices to determine the mechanism of the reduced synaptic strength. We find that size of miniature excitatory postsynaptic currents (mepscs) is unaffected by adenosine at concentrations up to 100 microM, an observation that indicates adenosine's mode of action is not through a decreased postsynaptic sensitivity to neurotransmitter. A quantal analysis indicates, however, that the quantity of neurotransmitter released is sufficiently diminished by adenosine to account entirely for the adenosine-produced decrease in synaptic strength. Application of 3-isobutyl-1-methylxanthine (IBMX), a drug that antagonizes the effects of endogenous adenosine, produces an increase in synaptic strength. This observation suggests that the resting level of adenosine in our slices is appreciable, and an analysis of the adenosine dose-response relation is consistent with endogenous adenosine levels of about 10 microM. IBMX application produces only slight changes in the amplitude of mepscs, whereas a quantal analysis demonstrates that the drug significantly increases the amount of neurotransmitter released. Thus IBMX acts as an "anti-adenosine" in our experiments. In some experiments we have been able to record excitatory and inhibitory synaptic currents produced by the same perforant path stimulus. In these instances we find that inhibitory transmission is unaffected by concentrations of adenosine that produce a marked decrease in the strength of excitatory synapses.
Topics: 1-Methyl-3-isobutylxanthine; Adenosine; Animals; Dose-Response Relationship, Drug; Electric Conductivity; Hippocampus; In Vitro Techniques; Membrane Potentials; Rats; Synapses; Synaptic Transmission
PubMed: 1382294
DOI: 10.1073/pnas.89.18.8586 -
Iowa Medicine : Journal of the Iowa... Jan 1992Adenosine (Adenocard) is a new injectable antiarrhythmic agent indicated for the acute treatment of paroxysmal supraventricular tachycardia (PSVT) including PSVT... (Review)
Review
Adenosine (Adenocard) is a new injectable antiarrhythmic agent indicated for the acute treatment of paroxysmal supraventricular tachycardia (PSVT) including PSVT associated with the Wolff-Parkinson-White syndrome. Many physicians are not yet familiar with its actions, indications and side effects.
Topics: Adenosine; Humans
PubMed: 1735634
DOI: No ID Found -
PloS One 2015Adenosine is a powerful trigger for ischemic preconditioning (IPC). Myocardial ischemia induces intracellular and extracellular ATP degradation to adenosine, which then...
BACKGROUND
Adenosine is a powerful trigger for ischemic preconditioning (IPC). Myocardial ischemia induces intracellular and extracellular ATP degradation to adenosine, which then activates adenosine receptors and elicits cardioprotection. Conventionally extracellular adenosine formation by ecto-5'-nucleotidase (CD73) during ischemia was thought to be negligible compared to the massive intracellular production, but controversial reports in the past demand further evaluation. In this study we evaluated the relevance of ecto-5'-nucleotidase (CD73) for infarct size reduction by ischemic preconditioning in in vitro and in vivo mouse models of myocardial infarction, comparing CD73-/- and wild type (WT) mice.
METHODS AND RESULTS
3x5 minutes of IPC induced equal cardioprotection in isolated saline perfused hearts of wild type (WT) and CD73-/- mice, reducing control infarct sizes after 20 minutes of ischemia and 90 minutes of reperfusion from 46 ± 6.3% (WT) and 56.1 ± 7.6% (CD73-/-) to 26.8 ± 4.7% (WT) and 25.6 ± 4.7% (CD73-/-). Coronary venous adenosine levels measured after IPC stimuli by high-pressure liquid chromatography showed no differences between WT and CD73-/- hearts. Pharmacological preconditioning of WT hearts with adenosine, given at the measured venous concentration, was evenly cardioprotective as conventional IPC. In vivo, 4x5 minutes of IPC reduced control infarct sizes of 45.3 ± 8.9% (WT) and 40.5 ± 8% (CD73-/-) to 26.3 ± 8% (WT) and 22.6 ± 6.6% (CD73-/-) respectively, eliciting again equal cardioprotection. The extent of IPC-induced cardioprotection in male and female mice was identical.
CONCLUSION
The infarct size limiting effects of IPC in the mouse heart in vitro and in vivo are not significantly affected by genetic inactivation of CD73. The ecto-5'-nucleotidase derived extracellular formation of adenosine does not contribute substantially to adenosine's well known cardioprotective effect in early phase ischemic preconditioning.
Topics: 5'-Nucleotidase; Adenosine; Animals; Disease Models, Animal; Extracellular Space; Female; Inosine; Ischemic Preconditioning, Myocardial; Male; Mice; Mice, Knockout; Myocardial Infarction; Myocardial Ischemia; Sex Factors; Ventricular Function, Left
PubMed: 26261991
DOI: 10.1371/journal.pone.0135086